ACETYLCYSTEINE
 DOSING INFORMATION
 1.4 PEDIATRIC DOSAGE
 1.4.1 NORMAL DOSE
 A. ORAL
 1. ACETAMINOPHEN POISONING
 a. The acute ingestion of acetaminophen in quantities of 150
milligrams/kilogram or greater may result in hepatic toxicity.
Acetylcysteine is most effective in preventing
acetaminophen-induced liver injury following overdose if
administered within 16 hours postingestion. Loading dose is
140 milligrams/kilogram orally followed by 70
milligrams/kilogram orally every 4 hours for 17 additional
doses (Peterson & Rumack, 1977; Peterson & Rumack,
1978).
 b. The manufacturer recommends that regardless of the
quantity of acetaminophen reported to have been ingested,
acetylcysteine should be administered if 24 hours or less
have elapsed from the time of the reported ingestion of an
overdose. Do not wait for the result of laboratory assays for
acetaminophen levels. The following procedures are
recommended (Prod Info Mucomyst(R), 1996):
 (1) The stomach should be emptied by lavage or
emesis with syrup of ipecac. Syrup of ipecac should
be given in a dose of 15 to 30 milliliters for children
and 30 to 40 milliliters for adults accompanied by 4
to 6 ounces of water. The dose should be repeated
if emesis does not occur in 20 minutes.
 (2) In the cases of a mixed drug overdose, activated
charcoal may be indicated. If activated charcoal is
administered, it is recommended that the patient be
lavaged before administration of acetylcysteine
since activated charcoal adsorbs acetylcysteine in
vitro and may also do so in vivo.
 (3) Blood should be drawn for acetaminophen
plasma assay and for baseline SGOT, SGPT,
bilirubin, prothrombin time, creatinine, BUN, blood
sugar, and electrolytes. Plasma or serum
acetaminophen concentrations should be
determined as early as possible but no sooner than
4 hours following acute overdose. These levels are
essential in assessing the potential risk of
hepatotoxicity. If an assay for acetaminophen
cannot be obtained, it is necessary to assume the
overdose is potentially toxic.
 (4) Administer the loading dose of acetylcysteine
(140 milligrams/kilogram of body weight).
 (5) Four hours after the loading dose, administer the
first maintenance dose of 70 milligrams/kilogram.
Maintenance doses should be repeated at 4-hour
intervals for a total of 17 doses unless the initial
acetaminophen assay reveals a nontoxic level.
 (6) If the patient vomits the loading dose or any
maintenance dose within 1 hour of administration,
repeat that dose. If the patient is persistently unable
to retain the acetylcysteine, it may be administered
by duodenal intubation.
 (7) Repeat SGOT, SGPT, bilirubin, prothrombin time,
creatinine, BUN, blood sugar, and electrolytes daily
if the acetaminophen plasma level is in the
potentially toxic range.
 2. MUCOLYTIC
 a. Children 6 to 14 years, 300 to 400 mg daily in 3 to 4
divided doses; and children 2 to 5 years of age, 200 to 300
mg daily in 2 to 3 divided doses (Fachinfo Fluimucil(R) akut,
1997).
 B. ORAL SOLUTION PREPARATION
 1. The 20% acetylcysteine solution should be diluted with cola drinks,
Fresca, or other soft drinks to a final concentration of 5%. If
administered via gastric tube or Miller-Abbott tube, water may be
used as the diluent. The dilution should be freshly prepared and
utilized within one hour.
 C. ORAL DOSAGE GUIDE AND PREPARATION
 1. Doses of oral acetylcysteine in relation to body weight are (Prod
Info Mucomyst(R), 1996):
LOADING DOSE**
AcetMuco- DiluTotal
ylcys- myst
ent
5% solteine
20%
(mL)
ution
(g)
(mL)
(mL)
--------------------------------------100-109 15
75
225
300
90-99
14
70
210
280
80-89
13
65
195
260
70-79
11
55
165
220
60-69
10
50
150
200
50-59
8
40
120
160
40-49
7
35
105
140
30-39
6
30
90
120
20-29
4
20
60
80
MAINTENANCE DOSE**
Weight
AcetMuco- DiluTotal
(kg)
ylcys- myst
ent
5% solteine
20%
(mL)
ution
(g)
(mL)
(mL)
--------------------------------------100-109 7.5
37
113
150
90-99
7
35
105
140
80-89
6.5
33
97
130
70-79
5.5
28
82
110
60-69
5
25
75
100
50-59
4
20
60
80
40-49
3.5
18
52
70
30-39
3
15
45
60
20-29
2
10
30
40
**If patient weighs less than 20 kg
(usually patients younger than 6
Weight
(kg)
years),
calculate the dose of Mucomyst(R).
Each milliliter of 20% Mycomyst(R)
contains
200 milligrams of acetylcysteine.
The
loading
dose is 140 milligrams/kilogram. The
maintenance
dose is 70 milligrams/kilogram. Three
(3) milliliters
of diluent are added to each milliliter
of 20% Mucomyst(R). Do not decrease
the
proportion of diluent.
 D. INTERPRETATION OF ACETAMINOPHEN ASSAY
 1. When results of the plasma acetaminophen assay are available, the
Rumack/Matthew nomogram (available in Mucomyst(R) package
inserts) should be utilized to determine if plasma concentrations are in
the potentially toxic range. Values above the solid line connecting 200
micrograms/milliliter at 4 hours with 50 micrograms/milliliter at 12
hours are associated with a possibility of hepatic toxicity if
acetylcysteine is not administered. If the plasma level is above the
broken line on the nomogram, continue with maintenance doses of
acetylcysteine. If the initial plasma level is below the broken line on
the nomogram, there is minimal risk of hepatic toxicity and
acetylcysteine treatment can be discontinued (Prod Info
Mucomyst(R), 1996).
 E. INTRAVENOUS
 1. ACETAMINOPHEN POISONING
 a. SUMMARY
 (1) There is NO FDA-approved commercially
available sterile, pyrogen-free, intravenous (IV)
formulation of acetylcysteine in the United States.
The oral/inhalation preparation is NOT officially
approved for IV use. Pyrogen-free intravenous
acetylcysteine is available investigationally ONLY
through participating poison centers. There are 2
intravenous protocols currently under investigation.
 (2) FORTY-EIGHT HOUR PROTOCOL: Dilute 20%
solution 1:5 in dextrose 5% in water (D5W) and give
slowly over one hour. If an adverse reaction occurs,
diphenhydramine is given and subsequent doses
are given over 2 hours. The initial dose is 140
milligrams/kilogram, followed by 70
milligrams/kilogram every 4 hours for a total of 13
doses (Smilkstein et al, 1991).
 (3) TWENTY HOUR PROTOCOL: Administer 150
milligrams/kilogram in 200 milliliters D5W over 15
minutes, followed by 50 milligrams/kilogram in 500
milliliters D5W over 4 hours, followed by 100
milligrams/kilogram in 1 liter D5W over the next 16
hours (Prescott et al, 1979; Westman, 1989).
 (4) There does appear to be a slight increased risk
of adverse reactions following intravenous
administration (primarily urticaria and/or
bronchospasm which are rate-related, but
anaphylactoid reactions have occurred).
 b. Intravenous acetylcysteine is safe and effective for
preventing the hepatic and renal toxicities following overdose
of acetaminophen (Prescott, 1981). Similar findings were
reported elsewhere (Shenfeld & Oh, 1980).
 c. Dosing information is as follows (Westman, 1989): Patients
who present with toxic levels of acetaminophen less than 10
hours after ingestion should receive acetylcysteine
intravenously for 20 hours (150 milligrams/kilogram of body
weight as a bolus dose, followed by 50 milligrams/kilogram
for 4 hours and then 100 milligrams/kilogram for 16 hours).
Patients who present with toxic levels of acetaminophen
more than 10 hours after ingestion should receive
acetylcysteine IV for 48 hours (150 milligrams/kilogram as a
bolus dose, followed by 50 milligrams/kilogram for 4 hours
and then 286 milligrams/kilogram for 44 hours).
Hemoperfusion may be of value and should be considered
for patients presenting early with toxic levels of
acetaminophen and severe acidosis, presenting early with
extremely high levels of acetaminophen (4000 nmol/liter or
more) and patients presenting more than 15 hours after the
ingestion with serum levels exceeding 1000 nmol/liter.
 F. INTRAVENOUS RATE OF ADMINISTRATION
 1. Adverse reactions to intravenous acetylcysteine appear to be ratedependent. Intravenous acetylcysteine should be administered slowly
over 1 hour; however if an adverse reaction occurs, diphenhydramine
is given and subsequent doses are given over 2 hours to minimize
complications (Smilkstein et al, 1991; Tenenbein, 1984).
 G. RECTAL
 1. ACETAMINOPHEN POISONING
 a. There are no reports of acetylcysteine being administered
rectally for treatment of acetaminophen poisoning. The extent
of its absorption via the rectum is not known (Pers Comm,
1983; Pers Comm, 1983a). Rectal administration of
acetylcysteine solution is not recommended for treatment of
acetaminophen overdose. For patients not able to retain oral
doses of acetylcysteine, administration of diluted doses via
nasogastric tube or by slow intravenous infusion may be
tried. An intravenous formulation of acetylcysteine is
available in the United States under an investigational
protocol through participating poison centers.
 2. MECONIUM ILEUS
 a. Acetylcysteine enemas together with acetylcysteine orally
have been used with apparent success in neonates,
children, and adults with bowel obstruction due to meconium
ileus or meconium ileus equivalent. A 4% to 6%
acetylcysteine enema (diluted in 100 to 300 milliliters of water
or normal saline) administered every 6 to 12 hours appears
to be effective and safe, but higher concentrations have
been used (Spiro, 1977; Hodson et al, 1976; Derman et al,
1975; Shaw, 1969; Simpson et al, 1968).
 H. RESPIRATORY ADMINISTRATION
 1. PULMONARY DISORDERS
 a. Acetylcysteine has been administered via tracheostomy,
intratracheal catheter, nebulizer, intermittent positive
pressure breathing (IPPB), endotracheal tube and cannula
(Webb, 1962). It is generally felt that direct instillation or
intermittent positive pressure breathing (IPPB) are much
superior to nebulization (Poppe, 1964; Miller, 1973). When
administered by direct instillation, 1 to 2 milliliters of a 10% to
20% solution may be given as often as every hour. When
used for the routine care of patients with tracheostomy, 1 to 2
milliliters of a 10% to 20% solution may be administered
every 1 to 4 hours by instillation into the tracheostomy (Prod
Info Mucomyst(R), 1996). A dosage of 2 to 5 milliliters of the
10% solution is as effective and produces less
bronchoconstriction than higher (20%) concentrations
(Hirsch & Kory, 1967).
 b. When nebulized into a face mask, mouth piece, or
tracheostomy, 1 to 10 milliliters of the 20% solution or 2 to 20
milliliters of the 10% solution may be given every 2 to 6
hours. The recommended dose for most patients is 3 to 5
milliliters of the 20% solution or 6 to 10 milliliters of the 10%
solution 3 to 4 times daily (Prod Info Mucomyst(R), 1996).
 c. The 20% solution may be diluted to a lesser concentration
with either sodium chloride for injection, sodium chloride for
inhalation, sterile water for injection, or sterile water for
inhalation. The 10% solution may be used undiluted. Any
unused portion of the solution should be stored in the
refrigerator and used within 96 hours (Prod Info
Mucomyst(R), 1996).
 d. For treatment of pulmonary complications of surgery or
posttraumatic chest conditions, 1 to 2 milliliters of 20%
acetylcysteine solution or 2 to 4 milliliters of 10% solution
may be given every 1 to 4 hours via a syringe attached to the
intratracheal catheter; 2 to 5 milliliters of the 20% solution
may be introduced with a syringe through a tracheal catheter
when contact with a particular segment of the
bronchopulmonary tree is desired (Prod Info Mucomyst(R),
1996; AHFS, 1989).